Mutation Research-Reviews in Mutation Research最新文献

{"title":"Novel insights into the role of ion channels in cellular DNA damage response","authors":"Kamila Maliszewska-Olejniczak,&nbsp;Piotr Bednarczyk","doi":"10.1016/j.mrrev.2024.108488","DOIUrl":"10.1016/j.mrrev.2024.108488","url":null,"abstract":"<div><p>The DNA damage response (DDR) is a complex and highly regulated cellular process that detects and repairs DNA damage. The integrity of the DNA molecule is crucial for the proper functioning and survival of cells, as DNA damage can lead to mutations, genomic instability, and various diseases, including cancer. The DDR safeguards the genome by coordinating a series of signaling events and repair mechanisms to maintain genomic stability and prevent the propagation of damaged DNA to daughter cells. The study of an ion channels in the context of DDR is a promising avenue in biomedical research. Lately, it has been reported that the movement of ions through channels plays a crucial role in various physiological processes, including nerve signaling, muscle contraction, cell signaling, and maintaining cell membrane potential. Knowledge regarding the involvement of ion channels in the DDR could support refinement of our approach to several pathologies, mainly cancer, and perhaps lead to innovative therapies. In this review, we focused on the ion channel's possible role in the DDR. We present an analysis of the involvement of ion channels in DDR, their role in DNA repair mechanisms, and cellular outcomes. By addressing these areas, we aim to provide a comprehensive perspective on ion channels in the DDR and potentially guide future research in this field. It is worth noting that the interplay between ion channels and the cellular DDR is complex and multifaceted. More research is needed to fully understand the underlying mechanisms and potential therapeutic implications of these interactions.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"793 ","pages":"Article 108488"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1383574224000012/pdfft?md5=4273466af8ee37ae24201aecf24cd5ae&pid=1-s2.0-S1383574224000012-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Super-enhancers: Implications in gastric cancer","authors":"Yizhou Huang ,&nbsp;Yanfei Huo ,&nbsp;Linying Huang ,&nbsp;Long Zhang ,&nbsp;Yanxiu Zheng ,&nbsp;Nasha Zhang ,&nbsp;Ming Yang","doi":"10.1016/j.mrrev.2024.108489","DOIUrl":"https://doi.org/10.1016/j.mrrev.2024.108489","url":null,"abstract":"<div><p>Gastric cancer (GC) is the fifth most prevalent malignancy and the third leading cause of cancer-related mortality globally. Despite intensive efforts to enhance the efficiencies of various therapeutics (chemotherapy, surgical interventions, molecular-targeted therapies, immunotherapies), the prognosis for patients with GC remains poor. This might be predominantly due to the limited understanding of the complicated etiology of GC. Importantly, epigenetic modifications and alterations are crucial during GC development. Super-enhancers (SEs) are a large cluster of adjacent enhancers that greatly activate transcription. SEs sustain cell-specific identity by enhancing the transcription of specific oncogenes. In this review, we systematically summarize how SEs are involved in GC development, including the SE landscape in GC, the SE target genes in GC, and the interventions related to SE functions for treating GC.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"793 ","pages":"Article 108489"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139731761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria act as a key regulatory factor in cancer progression: Current concepts on mutations, mitochondrial dynamics, and therapeutic approach","authors":"Sraddhya Roy ,&nbsp;Ananya Das ,&nbsp;Aparajita Bairagi ,&nbsp;Debangshi Das ,&nbsp;Ashna Jha ,&nbsp;Amit Kumar Srivastava ,&nbsp;Nabanita Chatterjee","doi":"10.1016/j.mrrev.2024.108490","DOIUrl":"10.1016/j.mrrev.2024.108490","url":null,"abstract":"<div><p>The diversified impacts of mitochondrial function vs. dysfunction have been observed in almost all disease conditions including cancers. Mitochondria play crucial roles in cellular homeostasis and integrity, however, mitochondrial dysfunctions influenced by alterations in the mtDNA can disrupt cellular balance. Many external stimuli or cellular defects that cause cellular integrity abnormalities, also impact mitochondrial functions. Imbalances in mitochondrial activity can initiate and lead to accumulations of genetic mutations and can promote the processes of tumorigenesis, progression, and survival. This comprehensive review summarizes epigenetic and genetic alterations that affect the functionality of the mitochondria, with considerations of cellular metabolism, and as influenced by ethnicity. We have also reviewed recent insights regarding mitochondrial dynamics, miRNAs, exosomes that play pivotal roles in cancer promotion, and the impact of mitochondrial dynamics on immune cell mechanisms. The review also summarizes recent therapeutic approaches targeting mitochondria in anti-cancer treatment strategies.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"793 ","pages":"Article 108490"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incorporating functional genomics into the pathology-supported genetic testing framework implemented in South Africa: A future view of precision medicine for breast carcinomas","authors":"Claudia Christowitz ,&nbsp;Daniel W. Olivier ,&nbsp;Johann W. Schneider ,&nbsp;Maritha J. Kotze ,&nbsp;Anna-Mart Engelbrecht","doi":"10.1016/j.mrrev.2024.108492","DOIUrl":"https://doi.org/10.1016/j.mrrev.2024.108492","url":null,"abstract":"<div><p>A pathology-supported genetic testing (PSGT) framework was established in South Africa to improve access to precision medicine for patients with breast carcinomas. Nevertheless, the frequent identification of variants of uncertain significance (VUSs) with the use of genome-scale next-generation sequencing has created a bottleneck in the return of results to patients. This review highlights the importance of incorporating functional genomics into the PSGT framework as a proposed initiative. Here, we explore various model systems and experimental methods available for conducting functional studies in South Africa to enhance both variant classification and clinical interpretation. We emphasize the distinct advantages of using <em>in vitro</em>, <em>in vivo</em>, and translational <em>ex vivo</em> models to improve the effectiveness of precision oncology. Moreover, we highlight the relevance of methodologies such as protein modelling and structural bioinformatics, multi-omics, metabolic activity assays, flow cytometry, cell migration and invasion assays, tube-formation assays, multiplex assays of variant effect, and database mining and machine learning models. The selection of the appropriate experimental approach largely depends on the molecular mechanism of the gene under investigation and the predicted functional effect of the VUS. However, before making final decisions regarding the pathogenicity of VUSs, it is essential to assess the functional evidence and clinical outcomes under current variant interpretation guidelines. The inclusion of a functional genomics infrastructure within the PSGT framework will significantly advance the reclassification of VUSs and enhance the precision medicine pipeline for patients with breast carcinomas in South Africa.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"793 ","pages":"Article 108492"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S138357422400005X/pdfft?md5=aa777804167f7a1c16e902b565a644ca&pid=1-s2.0-S138357422400005X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140632737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of genetic and epigenetic GNAS alterations in the development of early-onset obesity","authors":"Alaa Abbas ,&nbsp;Ayat S Hammad ,&nbsp;Mashael Al-Shafai","doi":"10.1016/j.mrrev.2023.108487","DOIUrl":"10.1016/j.mrrev.2023.108487","url":null,"abstract":"<div><h3>Background</h3><p><em>GNAS</em> (guanine nucleotide-binding protein, alpha stimulating) is an imprinted gene that encodes G_sα, the α subunit of the heterotrimeric stimulatory G protein. This subunit mediates the signalling of a diverse array of G protein-coupled receptors (GPCRs), including the melanocortin 4 receptor (MC4R) that serves a pivotal role in regulating food intake, energy homoeostasis, and body weight. Genetic or epigenetic alterations in <em>GNAS</em> are known to cause pseudohypoparathyroidism in its different subtypes and have been recently associated with isolated, early-onset, severe obesity. Given the diverse biological functions that G_sα serves, multiple molecular mechanisms involving various GPCRs, such as MC4R, β₂- and β₃-adrenoceptors, and corticotropin-releasing hormone receptor, have been implicated in the pathophysiology of severe, early-onset obesity that results from genetic or epigenetic <em>GNAS</em> changes.</p></div><div><h3>Scope of review</h3><p>This review examines the structure and function of <em>GNAS</em> and provides an overview of the disorders that are caused by defects in this gene and may feature early-onset obesity. Moreover, it elucidates the potential molecular mechanisms underlying G_sα deficiency-induced early-onset obesity, highlighting some of their implications for the diagnosis, management, and treatment of this complex condition.</p></div><div><h3>Major conclusions</h3><p>G_sα deficiency is an underappreciated cause of early-onset, severe obesity. Therefore, screening children with unexplained, severe obesity for <em>GNAS</em> defects is recommended, to enhance the molecular diagnosis and management of this condition.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"793 ","pages":"Article 108487"},"PeriodicalIF":5.3,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1383574223000352/pdfft?md5=090d4b148a016ca8a32bd7dec45a574d&pid=1-s2.0-S1383574223000352-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138683022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Congenital neutropenia: From lab bench to clinic bedside and back","authors":"Weronika Dobrewa,&nbsp;Marta Bielska,&nbsp;Katarzyna Bąbol-Pokora,&nbsp;Szymon Janczar,&nbsp;Wojciech Młynarski","doi":"10.1016/j.mrrev.2023.108476","DOIUrl":"10.1016/j.mrrev.2023.108476","url":null,"abstract":"<div><p>Neutropenia is a hematological condition characterized by a decrease in absolute neutrophil count (ANC) in peripheral blood, typically classified in adults as mild (1–1.5 × 10⁹/L), moderate (0.5–1 × 10⁹/L), or severe (&lt; 0.5 × 10⁹/L). It can be categorized into two types: congenital and acquired. Congenital severe chronic neutropenia (SCN) arises from mutations in various genes, with different inheritance patterns, including autosomal recessive, autosomal dominant, and X-linked forms, often linked to mitochondrial diseases. The most common genetic cause is alterations in the <em>ELANE</em> gene. Some cases exist as non-syndromic neutropenia within the SCN spectrum, where genetic origins remain unidentified. The clinical consequences of congenital neutropenia depend on granulocyte levels and dysfunction. Infants with this condition often experience recurrent bacterial infections, with approximately half facing severe infections within their first six months of life. These infections commonly affect the respiratory system, digestive tract, and skin, resulting in symptoms like fever, abscesses, and even sepsis. The severity of these symptoms varies, and the specific organs and systems affected depend on the genetic defect. Congenital neutropenia elevates the risk of developing acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), particularly with certain genetic variants. SCN patients may acquire <em>CSF3R</em> and <em>RUNX1</em> mutations, which can predict the development of leukemia. It is important to note that high-dose granulocyte colony-stimulating factor (G-CSF) treatment may have the potential to promote leukemogenesis. Treatment for neutropenia involves antibiotics, drugs that boost neutrophil production, or bone marrow transplants. Immediate treatment is essential due to the heightened risk of severe infections. In severe congenital or cyclic neutropenia (CyN), the primary therapy is G-CSF, often combined with antibiotics. The G-CSF dosage is gradually increased to normalize neutrophil counts. Hematopoietic stem cell transplants are considered for non-responders or those at risk of AML/MDS. In cases of WHIM syndrome, CXCR4 inhibitors can be effective. Future treatments may involve gene editing and the use of the diabetes drug empagliflozin to alleviate neutropenia symptoms.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"793 ","pages":"Article 108476"},"PeriodicalIF":5.3,"publicationDate":"2023-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1383574223000248/pdfft?md5=b700112fc36be06e1de57be90d4bfa4b&pid=1-s2.0-S1383574223000248-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138292263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comparison between mutational profiles in tumour tissue DNA and circulating tumour DNA in head and neck squamous cell carcinoma – A systematic review","authors":"Xiaomin Huang ,&nbsp;Paul Leo ,&nbsp;Lee Jones ,&nbsp;Pascal H.G. Duijf ,&nbsp;Gunter Hartel ,&nbsp;Lizbeth Kenny ,&nbsp;Sarju Vasani ,&nbsp;Chamindie Punyadeera","doi":"10.1016/j.mrrev.2023.108477","DOIUrl":"10.1016/j.mrrev.2023.108477","url":null,"abstract":"<div><h3>Background</h3><p>Head and neck cancer is the seventh most common malignancy globally. Head and neck squamous cell carcinoma (HNSCC) originates from squamous cells and 90% of HNC are HNSCC. The gold standard for diagnosing HNSCC is tissue biopsy. However, given tumour heterogeneity, biopsies may miss important cancer-associated molecular signatures, and more importantly, after the tumour is excised, there is no means of tracking response to treatment in patients. Captured under liquid biopsy, circulating tumour DNA (ctDNA), may identify in vivo molecular genotypes and complements tumour tissue analysis in cancer management. A systematic search was conducted in PubMed, Embase, Scopus and the Cochran Library between 2012 to early 2023 on ctDNA in HNSCC using publications written in English. We summarise 20 studies that compared mutational profiles between tumour tissue DNA (tDNA) and ctDNA, using a cohort of 631 HNSCC patients and 139 controls. Among these studies, the concordance rates varied greatly and the most mutated and the most concordant gene was <em>TP53,</em> followed by <em>PIK3CA, CDKN2A, NOTCH1</em> and <em>FAT1.</em> Concordant variants were mainly found in Stage IV tumours, and the mutation type is mostly single nucleotide variants (SNV). We conclude that, as a biomarker for HNSCC, ctDNA demonstrates great promise as it recapitulates tumour genotypes, however additional multi-central trials are needed.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"793 ","pages":"Article 108477"},"PeriodicalIF":5.3,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S138357422300025X/pdfft?md5=0b2d2421aae7730b8caf91d704d5628a&pid=1-s2.0-S138357422300025X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136400048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-generation sequencing methodologies to detect low-frequency mutations: “Catch me if you can”","authors":"Vijay Menon ,&nbsp;Douglas E. Brash","doi":"10.1016/j.mrrev.2023.108471","DOIUrl":"10.1016/j.mrrev.2023.108471","url":null,"abstract":"<div><p><span>Mutations, the irreversible changes in an organism’s DNA sequence, are present in tissues at a variant allele frequency (VAF) ranging from ∼10</span>^-8 per bp for a founder mutation to ∼10^-3<span> for a histologically normal tissue sample containing several independent clones – compared to 1%− 50% for a heterozygous tumor mutation or a polymorphism. The rarity of these events poses a challenge for accurate clinical diagnosis and prognosis, toxicology, and discovering new disease etiologies. Standard Next-Generation Sequencing (NGS) technologies report VAFs as low as 0.5% per nt, but reliably observing rarer precursor events requires additional sophistication to measure ultralow-frequency mutations. We detail the challenge; define terms used to characterize the results, which vary between laboratories and sometimes conflict between biologists and bioinformaticists; and describe recent innovations to improve standard NGS methodologies including: single-strand consensus sequence methods such as Safe-SeqS and SiMSen-Seq; tandem-strand consensus sequence methods such as o2n-Seq and SMM-Seq; and ultrasensitive parent-strand consensus sequence methods such as DuplexSeq, PacBio HiFi, SinoDuplex, OPUSeq, EcoSeq, BotSeqS, Hawk-Seq, NanoSeq, SaferSeq, and CODEC. Practical applications are also noted. Several methods quantify VAF down to 10</span>^-5 at a nt and mutation frequency (MF) in a target region down to 10^-7 per nt. By expanding to &gt; 1 Mb of sites never observed twice, thus forgoing VAF, other methods quantify MF &lt; 10^-9 per nt or &lt; 15 errors per haploid genome. Clonal expansion cannot be directly distinguished from independent mutations by sequencing, so it is essential for a paper to report whether its MF counted only different mutations – the minimum independent-mutation frequency MF_minI – or all mutations observed including recurrences – the larger maximum independent-mutation frequency MF_maxI which may reflect clonal expansion. Ultrasensitive methods reveal that, without their use, even mutations with VAF 0.5–1% are usually spurious.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"792 ","pages":"Article 108471"},"PeriodicalIF":5.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10273450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutagenesis-based plant breeding approaches and genome engineering: A review focused on tomato","authors":"Durre Shahwar ,&nbsp;Namju Ahn ,&nbsp;Donghyun Kim ,&nbsp;Wooseong Ahn ,&nbsp;Younghoon Park","doi":"10.1016/j.mrrev.2023.108473","DOIUrl":"10.1016/j.mrrev.2023.108473","url":null,"abstract":"<div><p><span>Breeding is the most important and efficient method for crop improvement involving repeated modification of the genetic makeup of a plant population over many generations. In this review, various accessible breeding approaches, such as conventional breeding and mutation breeding (physical and chemical </span>mutagenesis<span><span> and insertional mutagenesis), are discussed with respect to the actual impact of research on the economic improvement of tomato agriculture. Tomatoes are among the most economically important fruit crops consumed worldwide because of their high nutritional content and health-related benefits. Additionally, we summarize mutation-based mapping approaches, including Mutmap and MutChromeSeq, for the efficient mapping of several genes identified by random indel mutations that are beneficial for crop improvement. Difficulties and challenges in the adaptation of new genome editing techniques that provide opportunities to demonstrate precise mutations are also addressed. Lastly, this review focuses on various effective and convenient genome editing tools, such as RNA interference (RNAi), zinc finger </span>nucleases<span> (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR/Cas9), and their potential for the improvement of numerous desirable traits to allow the development of better varieties of tomato and other horticultural crops.</span></span></p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"792 ","pages":"Article 108473"},"PeriodicalIF":5.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10273453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Error-corrected next generation sequencing – Promises and challenges for genotoxicity and cancer risk assessment","authors":"Francesco Marchetti ,&nbsp;Renato Cardoso ,&nbsp;Connie L. Chen ,&nbsp;George R. Douglas ,&nbsp;Joanne Elloway ,&nbsp;Patricia A. Escobar ,&nbsp;Tod Harper Jr ,&nbsp;Robert H. Heflich ,&nbsp;Darren Kidd ,&nbsp;Anthony M. Lynch ,&nbsp;Meagan B. Myers ,&nbsp;Barbara L. Parsons ,&nbsp;Jesse J. Salk ,&nbsp;Raja S. Settivari ,&nbsp;Stephanie L. Smith-Roe ,&nbsp;Kristine L. Witt ,&nbsp;Carole L. Yauk ,&nbsp;Robert Young ,&nbsp;Shaofei Zhang ,&nbsp;Sheroy Minocherhomji","doi":"10.1016/j.mrrev.2023.108466","DOIUrl":"10.1016/j.mrrev.2023.108466","url":null,"abstract":"<div><p>Error-corrected Next Generation Sequencing (ecNGS) is rapidly emerging as a valuable, highly sensitive and accurate method for detecting and characterizing mutations in any cell type, tissue or organism from which DNA can be isolated. Recent mutagenicity and carcinogenicity studies have used ecNGS to quantify drug-/chemical-induced mutations and mutational spectra associated with cancer risk. ecNGS has potential applications in genotoxicity assessment as a new readout for traditional models, for mutagenesis studies in 3D organotypic cultures, and for detecting off-target effects of gene editing tools. Additionally, early data suggest that ecNGS can measure clonal expansion of mutations as a mechanism-agnostic early marker of carcinogenic potential and can evaluate mutational load directly in human biomonitoring studies. In this review, we discuss promising applications, challenges, limitations, and key data initiatives needed to enable regulatory testing and adoption of ecNGS – including for advancing safety assessment, augmenting weight-of-evidence for mutagenicity and carcinogenicity mechanisms, identifying early biomarkers of cancer risk, and managing human health risk from chemical exposures.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"792 ","pages":"Article 108466"},"PeriodicalIF":5.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10135638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}